4,724 research outputs found

    Transcription Factor AP-2 Regulatory Signatures in Breast Cancer

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    PhDAP-2 transcription factors are highly conserved basic helix-span-helix proteins whose members ((x, ß, y, S and c) are crucial regulators of bryonic development. They also play an important role in human neoplasia. uohis ochemical studies have detected high levels of AP-2y expression in primary tumo of breast cancer patients. This high expression has been correlated with reduced survival in all patients and reduced survival in an ERa positive subset treated with hormone therapy. In breast cancer cell lines, AP- 2 factors have been implicated in the regulation of the ERBB2 proto-oncogene and ERa. In an effort to further understand the role of AP-2y in breast carcinoma, this study has sought to identify additional AP-2 activated cellular pathways and ultimately novel transcriptional targets for AP-2 through the use of gene expression profiling. RNAi using three independent AP-2y targeting sequences, has been used to deplete AP- 2y levels in the ERa positive MCF-7 breast carcinoma cell line, chosen as it exclusively expresses the AP-2y family member. Microarrays were then utilised to create an AP-2y dependent transcription profile. Statistical comparisons between non-silencing control siRNA and AP-2y targeting siRNA groups identified a total of 162 gene expression changes (p<0.01). These changes implicate AP-2y in the control of cell cycle progression and developmental signalling. Indeed a role for AP-2y in the control of cell cycle, in particular at the GUS transition, has been verified using flow cytometry. Several of these gene expression changes, including IGFBP3, Transgelin and KIAA1324, have been confirmed using qPCR and immunoblotting. Finally, elevated levels of p21 mRNA and protein have been observed following AP-2y silencing in MCF-7 cells. Additionally, the activity of a p21 promoter reporter is repressed following transfection with an AP-2y expression construct in HepG2 cells. These results coupled with ChIP experiments showing AP-2y occupancy at the proximal promoter region of p21 in cycling MCF-7 cells, implicate AP-2y in the repression of p21 transcription and suggest a role for AP2y in- the, control of cell cycle in breast carcinoma in part through the transcriptional repression of p21

    AP Literature Summer Reading Unit for My Antonia and Adventures of Huckleberry Finn [12th grade]

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    This is an approximately four week unit intended for senior AP Literature students with daily forty five minute class periods. It is based on the novels My Antonia by Willa Cather, and Adventures of Huckleberry Finn by Mark Twain. These novels were both summer reading assignments, so the students should have read them previously during the summer and completed assignments based on them before the unit begins. This unit will be the first one of the year, after about a week of assignments focused on getting to know the students and teambuilding. Due to the fact that the novels have already been read, this unit goals focus on helping students acquire meaning from them, and on helping them lay the foundation for AP Literature curriculum with timed writings, Socratic Seminar, and open ended AP essay practice. The first two weeks are spent on My Antonia. After collecting and reviewing the summer reading questions, we begin on class dialogues designed to help students unpack the text, connect their reading to themes, and become better at close reading and analysis. Afterwards I introduce Levels of Questioning and Socratic Seminar, which will be meaning and analysis tools we continue to use in every unit this year. Next I introduce timed writing strategies, and the students do their first timed writing practice of the year, which is scaffolded as it is based off of previous class dialogue. The students then use that timed writing as a basis for revision and editing with peer and teacher feedback, which gives them practice and helps them expand and enhance their original responses. The second two weeks are spent on Adventures of Huckleberry Finn. We begin by comparing and contrasting the two summer reading novels with Pride and Prejudice, which is a novel they have read in a previous year. In this we focus on structure (form) and purpose (function) of the novel, which will help them in their analysis of this and future text. We continue with more reading dialogues and activities, and then a scaffolded revision of their Summer Reading Essay over Adventures of Huckleberry Finn where they receive feedback from the teacher. We finish with a second Socratic Seminar, and a final independent Timed Writing Essay where they show their transfer of thematic textual analysis and AP timed writing skills. After this unit is completed, students should come away with understandings about how the past, our surroundings, and society can affect us, as well as increased knowledge and skill in Socratic Seminar skills, timed writing, and crafting AP style essays

    The Treatment of Ties in AP Correlation

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    The Kendall tau and AP correlation coefficients are very commonly use to compare two rankings over the same set of items. Even though Kendall tau was originally defined assuming that there are no ties in the rankings, two alternative versions were soon developed to account for ties in two different scenarios: measure the accuracy of an observer with respect to a true and objective ranking, and measure the agreement between two observers in the absence of a true ranking. These two variants prove useful in cases where ties are possible in either ranking, and may indeed result in very different scores. AP correlation was devised to incorporate a top-heaviness component into Kendall tau, penalizing more heavily if differences occur between items at the top of the rankings, making it a very compelling coefficient in Information Retrieval settings. However, the treatment of ties in AP correlation remains an open problem. In this paper we fill this gap, providing closed analytical formulations of AP correlation under the two scenarios of ties contemplated in Kendall tau. In addition,we developed an R package that implements these coefficients.Best Short Paper Accepted author manuscriptMultimedia ComputingWeb Information System

    Dividend cuts, firm profitability and financial characteristics

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    This paper investigates the dividend decisions of firms in the UK reporting losses after sustained periods of profitability. It is found that loss-making firms are more likely to reduce dividends compared to firms that remain profitable, although a loss is far from a guarantee that the dividend payment will be reduced. A lower propensity to reduce dividends is found in the UK relative to the US, consistent with the stronger culture of dividend payments. The size of the loss is an important factor in a firm’s dividend policy. However, this is mitigated to some extent if it is the result of unusual accounting items because managers view these as a temporary fluctuation in profitability. Leverage is found to have some role in the dividend decision, with higher levels of debt consistent with a greater likelihood of a reduction in the distribution whilst also suppressing profitability in future years. Profit margins prior to the loss year are also a significant factor in dividend policy whereby low margin firms are more likely to cut dividends

    Delamination Analysis of A Class of AP-PLY Composite Laminates

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    A recently developed fiber placement architecture, AP-PLY, has been shown to give significantly improved damage tolerance characteristics of composite structures. The behavior of delaminations resulting from low speed impact damage is of particular concern. Major attention has been paid to expand current knowledge on the delamination response of simple AP-PLY composite structure and move towards in-depth understanding of the failure mechanisms behind the damage tolerance. This thesis presents the approaches to predict delamination onset and analyze delamination growth, in support of the search of the optimum woven pattern for AP-PLY composite laminates. The recovered interlaminar stress between layers combined with the maximum stress criterion determined the delamination onset of simple AP-PLY composite laminate under out-of-plane loads. 2D finite element models with cohesive elements inserted in the interfaces of woven layers have been built to evaluate the delamination initiation and propagation in the different woven patterns of simple AP-PLY composite beams. The parameters of the woven pattern, such as the woven angle, the number of woven plies, the number of straight filled plies, and the location of the woven patterns in through the thickness direction, were investigated and shown to have a significant effect on delamination creation and growth. An energy method based on beam theory was proposed to analyze the strain energy release rate (SERR) of an existing crack in an AP-PLY beam structure. The developed analytical method was implemented in isotropic materials and the obtained SERR of a crack was validated by reference results and finite element solutions. The general behavior of crack growth on the left or right crack tip was evaluated and basic trends leading to crack propagation on one side of the crack were established. A correction factor was introduced to improve the accuracy of the SERR of a small crack through the numerical calculation. The singularity of crack tip caused by dissimilar materials was investigated and was found that the inclusion of the singularity effect could increase the accuracy for small cracks. It has been shown that the neutral axis needs to be relocated to decouple the bending and membrane behavior of unsymmetrical composite laminates, thus to meet the requirement of minimizing the strain energy of the delaminated beam to calculate the SERR of a delaminated composite beam. The calculated SERR of a crack in a composite beam has been verified by comparing with a finite element model. The woven plies in AP-PLY composite laminate altered the layup and two conventional laminates with different stacking sequences were identified in an AP-PLY composite laminate based on the assumption that the resin areas were ignored. A step by step approach was developed to obtain the SERR of a crack that goes across different materials. The analytical SERR determined when two materials are used in sequence, sets the stage for optimization of AP-PLY composite laminates without taking account of the effect of the resin area. The procedure of optimization of simple AP-PLY pattern was proposed and industry may benefit for many applications. An equivalent stiffness approach was used to model regions containing resin pockets and straight or inclined composite layers. A series of three point bending tests was carried out where the failure process and loading capacity were evaluated. The methodology, procedure of optimization, philosophy outlined in this thesis might also be applied to the more complicated fully woven AP-PLY composite laminates. The work in this thesis contributes to the understanding of the behavior of AP-PLY composite laminates with delaminations

    International evidence on payout ratio, returns. earnings and dividends

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    Recent US evidence has shown that, contrary to popular wisdom, the greater the proportion of earnings paid out as dividends, the greater the subsequent real earnings growth. We extend previous work by examining whether a similar relationship exists in eleven international markets as well as considering the role payout ratio plays in explaining future real dividend growth and returns. Higher payout ratios do indeed lead to higher real earnings growth, although not to higher real dividend growth. Despite the ability to anticipate earnings growth, we find limited use for this to predict future returns

    Structure function analysis of blazars AP Librae and 3c279

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    Highest Honors in AstronomyBlazars AP Librae and 3c279 are analyzed for microvariability using a technique known as structure function analysis. AP Librae was observed in April of 2005 and 3c279 was observed in April of 2007. The data for AP Librae was previously reduced by Andrew Collazzi and the author reduced the data for 3c279. Both sets of data were reduced using Robert Knop's data reduction program. The author ran structure function analysis on both sets of data. Structure function analysis is a statistical analysis run on data that is suppose to nd timescales of variability, periodicity, and the noise type of data. Previous analysis of AP Librae confirmed mircrovariability, which also shows up in the structure function of AP Librae. Blazar 3c279 was much quieter than AP Librae and showed no microvariability durning any of the nights.College of Arts and ScienceDepartment of Physics and Astronom

    Argus II retinal prosthesis system: a review of patient selection criteria, surgical considerations, and post-operative outcomes

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    Avni P Finn, Dilraj S Grewal, Lejla Vajzovic Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA Abstract: Retinitis pigmentosa (RP) is a group of heterogeneous inherited retinal degenerative disorders characterized by progressive rod and cone dysfunction and ensuing photoreceptor loss. Many patients suffer from legal blindness by their 40s or 50s. Artificial vision is considered once patients have lost all vision to the point of bare light perception or no light perception. The Argus II retinal prosthesis system is one such artificial vision device approved for patients with RP. This review focuses on the factors important for patient selection. Careful pre-operative screening, counseling, and management of patient expectations are critical for the successful implantation and visual rehabilitation of patients with the Argus II device. Keywords: retinal prosthesis, vision rehabilitation, artificial vision, patient selection, retinitis pigmentosa, retinal degeneration, low visio

    AP-based wireless intrusion detection systems

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    This thesis was scanned from the print manuscript for digital preservation and is copyright the author. Researchers can access this thesis by asking their local university, institution or public library to make a request on their behalf. Monash staff and postgraduate students can use the link in the References field

    Environmental toxicity, redox signaling and lung inflammation:the role of glutathione

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    Glutathione (gamma-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H(2)O(2) as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox-sensitive transcription factors such as Nrf2, NF-kappaB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation of GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-l-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease
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